Abstract

Colorectal cancer, the third most common cancer in both men and women, has gradually increased in recent years. MYSM1has been investigated as a regulator of hematopoiesis and lymphocyte development in human. It has been reported that some tumor-related genes were modulated by MYSM1. However, its exact role in cancer development remains unclear. Herein, we aimed to examine the expression level of MYSM1 in tumor tissues and its correlation with clinicopathology and survivals of patients with colorectal cancer (CRC).MYSM1expressions in tumor specimens resected from 123 CRC patients were detected by immunochemistry and Western blot analysis. The results showed that MYSM1 was significantly highly expressed in carcinoma tissues compared with adjacent normal mucosa tissues (P<0.05). Correlation analyses by Pearson’s chi-square test demonstrated that MYSM1 in tumors was positively correlated with tumor status (pathological assessment of the primary tumor (pT, P<0.001), regional lymph nodes (pN, P = 0.013), distant metastasis (pM, P<0.001)) and clinic stage (P<0.001); Whereas, MYSM1 was not associated with tumor size of CRC patients and was positively associated with tumor differentiation grade (P = 0.015). Patients with positiveMYSM1expression showed poor survival compared with the MYSM1 negative group (P<0.001).Simultaneously, multivariate Cox regression analysis indicated thatMYSM1 expression in tumor cells was an independent factor for reduced overall survival in CRC patients (P<0.001).Additionally,MYSM1 in CRC SW480 cells was silenced by small interference RNA (siRNA) technology. Scratch assay and Transwell assay showed that MYSM1 silencing decreased migration and invasion abilities of SW480 cells. These data suggested that expression of MYSM1 was associated with the progression of CRC and might be a potential biomarker for clinical prognosis.

Highlights

  • The prevalence of colorectal cancer (CRC), one of the most common cancers, has gradually increased in recent years

  • Protein levels of Myb-like SWIRM and MPN domains 1 (MYSM1) in normal mucosa (n = 30) and primary carcinoma (n = 30) tissues from CRC patients were detected by immunohistochemical staining

  • Western blot analysis was used to detect MYSM1 protein levels in patient tissues and showed the identical results to immunohistochemical staining (Fig 3A and 3B).These results suggest that MYSM1 is involved in tumorigenesis and metastasis of CRC

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Summary

Introduction

The prevalence of colorectal cancer (CRC), one of the most common cancers, has gradually increased in recent years. MYSM1 is an epigenetic regulator essential for the maintenance of hematopoietic stem cell (HSC) function, hematopoietic progenitor survival, and lymphocyte development. The loss of MYSM1 in mice contributes to severe hematopoietic dysfunction, the arrest of lymphocyte development and impaired multipotent progenitors (MPPs) survival[2,3,4].MYSM1 acts by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes [1]. It has been found that MYSM1-deficience-triggered impairment in hematopoieticstem cell (HSC) function is associated with the elevated tumor suppressor protein p53 expression [2,4]. It has been reported that p53 is activated in MYSM1-deficient mice and stimulates the upregulation of p53-induced mediators of apoptosis, leading to hematopoietic defects and cell cycle arrest [5]. The clinical significance of MYSM1 in CRC has not yet been reported

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